DESCRIPTION: (Applicant's Abstract) Because cocaine use remains epidemic among most opioid maintenance programs and pharmacological therapeutic strategies specifically aimed at cocaine's dopaminergic actions have shown little efficacy in unselected populations, this proposal will examine a novel pharmacological strategy for treating cocaine abuse in opioid-maintained cocaine abusers; i.e., treatment with disulfiram. Specifically, the aim of this proposal is to examine the effects of disulfiram (0, 62.5, 125, or 250mg /day) on treatment outcome in methadone-maintained cocaine abusers. This 14-wk, double blind, randomized clinical trial will provide treatment for 160 opioid- and cocaine-dependent individuals (18-65 years). Participants will be placed on methadone maintenance during weeks 1-2, at which time level of cocaine use is assessed. Then participants will continue on methadone maintenance and be randomly assigned to receive one of the following doses of disulfiram: 0, 62.5, 125, or 250 mg/day. During stabilization on methadone (wks 1-2), participants typically are administered increasing doses of methadone on a daily basis until maintenance doses are attained. Then during the treatment phase (weeks 5-14), participants continue to receive their daily maintenance doses of methadone. In addition, they receive disulfiram/placebo on a daily basis. At the end the study, participants will undergo detoxification from methadone over a 4-week period. In order to enhance outcome, all participants receive weekly 1-hour psychotherapy (Cognitive Behavioral Treatment) with experienced clinicians specifically trained to deliver the therapy and who will receive ongoing supervision. The primary outcomes will be retention and reduction in opioid and cocaine use, as assessed by self-report and confirmed by thrice-weekly urinalyses. Secondary outcomes will include reductions in other illicit drug and alcohol use, as well as improvements in psychosocial functioning. The prognostic relevance of genotype at the dopamine beta-hydroxylase locus, dopamine beta-hydroxylase enzyme activity, and severity of cocaine dependence will also be examined.